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The host adherens junction molecule nectin-1 is downregulated in Chlamydia trachomatis-infected genital epithelial cells

Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA

Correspondence
Robert V. Schoborg
schoborg{at}etsu.edu

Nectin-1, a member of the immunoglobulin superfamily, is a Ca²⁺-independent cell adhesion protein implicated in the organization of E-cadherin-based adherens junctions (AJs) and claudin-based tight junctions (TJs) in epithelial cells. Nectin-1 also regulates cell–cell adhesion and cell polarization in a Cdc42- and Rac-dependent manner. Western blot analyses demonstrated that accumulation of host nectin-1 is decreased by 85 % at 48 hours post-infection (h.p.i.) in Chlamydia trachomatis serovar E-infected HeLa cells. Time-course experiments demonstrated that this decrease was sustained to 60 h.p.i. Nectin-1 downregulation in C. trachomatis-infected cells was prevented by both chloramphenicol exposure and prior inactivation of the chlamydiae with UV light, demonstrating that active C. trachomatis replication was required. Penicillin G-exposure studies demonstrated that nectin-1 accumulation was also altered during persistent infection. Finally, RT-PCR analyses indicated that chlamydial infection did not alter accumulation of any nectin-1 transcripts, demonstrating that nectin-1 accumulation is reduced at a post-transcriptional level. Intesrestingly, N-cadherin-dependent cell–cell junctions can be disrupted by C. trachomatis infection, as reported by Prozialeck et al. (2002). Because interaction of nectin molecules on adjacent cells is essential for AJ formation, these data suggest that C. trachomatis may disrupt AJs, at least in part, by diminishing nectin-1 accumulation. Notably, release of chlamydiae-infected epithelial cells has been observed both in vitro from polarized monolayers and in vivo from tissues, suggesting that chlamydia-modulated downregulation of adhesion molecules and the subsequent disruption of host cell adherence may be involved in chlamydial dissemination or pathogenesis.

Three supplementary figures (with references) showing the protein detected by nectin-1 antibodies CK6 and CK8, changes in nectin-1 accumulation in C. trachomatis-infected polarized HeLa cells and the potential role of nectin-1 downregulation in C. trachomatis dissemination within the host genital tract, and a supplementary table listing RT-PCR primers and positive control oligonucleotides, are available with the online version of this paper.